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PLoS Pathog. 2008 Jul 18;4(7):e1000108. doi: 10.1371/journal.ppat.1000108.

MDA-5 recognition of a murine norovirus.

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  • 1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.

Erratum in

  • PLoS Pathog. 2008 Oct;4(10). doi:10.1371/annotation/3ce83911-9ccf-4452-a690-2816d0e94c10.. Virgin Iv, Herbert W [corrected to Virgin, Herbert W].


Noroviruses are important human pathogens responsible for most cases of viral epidemic gastroenteritis worldwide. Murine norovirus-1 (MNV-1) is one of several murine noroviruses isolated from research mouse facilities and has been used as a model of human norovirus infection. MNV-1 infection has been shown to require components of innate and adaptive immunity for clearance; however, the initial host protein that recognizes MNV-1 infection is unknown. Because noroviruses are RNA viruses, we investigated whether MDA5 and TLR3, cellular sensors that recognize dsRNA, are important for the host response to MNV-1. We demonstrate that MDA5-/- dendritic cells(DC) have a defect in cytokine response to MNV-1. In addition, MNV-1 replicates to higher levels in MDA5-/- DCs as well as in MDA5-/- mice in vivo. Interestingly, TLR3-/- DCs do not have a defect in vitro, but TLR3-/- mice have a slight increase in viral titers. This is the first demonstration of an innate immune sensor for norovirus and shows that MDA5 is required for the control of MNV-1 infection. Knowledge of the host response to MNV-1 may provide keys for prevention and treatment of the human disease.

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